Tiao G, Lieberman M, Fischer J E, Hasselgren P O
Department of Surgery, University of Cincinnati, Ohio 45267-0558, USA.
Am J Physiol. 1997 Mar;272(3 Pt 2):R849-56. doi: 10.1152/ajpregu.1997.272.3.R849.
We tested the hypothesis that the difference in the response to sepsis of protein breakdown between fast- and slow-twitch skeletal muscle reflects differential activation of the energy-ubiquitin-dependent proteolytic pathway. In addition, we defined the time course and the tissue specificity of sepsis-induced changes in the expression of the ubiquitin pathway. Sepsis was induced in rats by cecal ligation and puncture; control rats were sham operated. Energy-dependent protein breakdown was measured in incubated extensor digitorum longus (EDL) and soleus muscles. Ubiquitin mRNA levels were determined by Northern blot analysis. Sepsis resulted in increased energy-dependent protein breakdown and upregulated expression of ubiquitin mRNA in the fast-twitch EDL but not in the slow-twitch soleus muscle. The sepsis-induced increase in ubiquitin mRNA levels in the EDL muscle was noticeable before the increase in energy-dependent protein breakdown. Sepsis increased ubiquitin mRNA levels in the diaphragm (a mixed fiber-type muscle) but not in heart, liver, kidney, or intestine, consistent with a tissue-specific regulation of the ubiquitin system during sepsis. The results suggest that the difference in protein breakdown during sepsis between fast- and slow-twitch muscles reflects differential activation of the energy-ubiquitin-dependent proteolytic pathway. The data also suggest that the expression of the ubiquitin pathway is upregulated in a time-dependent fashion during sepsis and that this response is not a generalized phenomenon but is tissue specific.
我们验证了这样一个假设，即快肌和慢肌骨骼肌对脓毒症蛋白质分解反应的差异反映了能量 - 泛素依赖性蛋白水解途径的不同激活情况。此外，我们确定了脓毒症诱导的泛素途径表达变化的时间进程和组织特异性。通过盲肠结扎和穿刺在大鼠中诱导脓毒症；对照大鼠进行假手术。在孵育的趾长伸肌（EDL）和比目鱼肌中测量能量依赖性蛋白分解。通过Northern印迹分析确定泛素mRNA水平。脓毒症导致快肌EDL中能量依赖性蛋白分解增加以及泛素mRNA表达上调，但在慢肌比目鱼肌中未出现这种情况。在能量依赖性蛋白分解增加之前，脓毒症诱导的EDL肌肉中泛素mRNA水平的增加就已很明显。脓毒症使膈肌（一种混合纤维类型的肌肉）中的泛素mRNA水平升高，但在心脏、肝脏、肾脏或肠道中未升高，这与脓毒症期间泛素系统的组织特异性调节一致。结果表明，脓毒症期间快肌和慢肌之间蛋白质分解的差异反映了能量 - 泛素依赖性蛋白水解途径的不同激活情况。数据还表明，脓毒症期间泛素途径的表达以时间依赖性方式上调，并且这种反应不是普遍现象，而是具有组织特异性。
